• Home
  • Search Results
  • Exercise, but Not Metformin Prevents Loss of Muscle Function Due to Doxorubicin in Mice Using an In Situ Method.

Exercise, but Not Metformin Prevents Loss of Muscle Function Due to Doxorubicin in Mice Using an In Situ Method.

International journal of molecular sciences (2021-09-11)
Amy D Mackay, Erik D Marchant, Makensie Louw, David M Thomson, Chad R Hancock

Though effective in treating various types of cancer, the chemotherapeutic doxorubicin (DOX) is associated with skeletal muscle wasting and fatigue. The purpose of this study was to assess muscle function in situ following DOX administration in mice. Furthermore, pre-treatments with exercise (EX) or metformin (MET) were used in an attempt to preserve muscle function following DOX. Mice were assigned to the following groups: control, DOX, DOX + EX, or DOX + MET, and were given a single injection of DOX (15 mg/kg) or saline 3 days prior to sacrifice. Preceding the DOX injection, DOX + EX mice performed 60 min/day of running for 5 days, while DOX + MET mice received 5 daily oral doses of 500 mg/kg MET. Gastrocnemius-plantaris-soleus complex function was assessed in situ via direct stimulation of the sciatic nerve. DOX treatment increased time to half-relaxation following contractions, indicating impaired recovery (p < 0.05). Interestingly, EX prevented any increase in half-relaxation time, while MET did not. An impaired relaxation rate was associated with a reduction in SERCA1 protein content (p = 0.07) and AMPK phosphorylation (p < 0.05). There were no differences between groups in force production or mitochondrial respiration. These results suggest that EX, but not MET may be an effective strategy for the prevention of muscle fatigue following DOX administration in mice.

Product Number
Product Description

Ponceau S, BioReagent, suitable for electrophoresis
Peroxidase from horseradish, Type II, essentially salt-free, lyophilized powder, 150-250 units/mg solid (using pyrogallol)
Sodium succinate dibasic hexahydrate, ReagentPlus®, ≥99%
Doxorubicin hydrochloride, suitable for fluorescence, 98.0-102.0% (HPLC)
Carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone, ≥98% (TLC), powder
Saponin, for molecular biology, used as non-ionic surfactant
Metformin hydrochloride, Pharmaceutical Secondary Standard; Certified Reference Material
L-(−)-Malic acid, ≥95% (titration)
L-Glutamic acid monosodium salt hydrate, ≥99% (HPLC), powder
Cytochrome c from bovine heart, ≥95% based on Mol. Wt. 12,327 basis
Antimycin A from Streptomyces sp.
Rotenone, ≥95%